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Stephen Friend (seated) and Eric Schadt (onscreen).

What if the best clues to curing genetic illness are not in the disease genes themselves, but in the resilient genes of those who who somehow don’t become ill?

That’s the idea of a new research study launched yesterday by open science advocate Stephen Friend president of Sage Bionetworks, along with an article in Science, the research journal, and a TED talk explaining the project. Friend and his colleagues hope to hunt through more than a million people in order to find a few who have genetic variants that should have killed them in childhood, but who have made it to age 30 or older.

“Maybe we’ve been looking too long at those who are sick,” says Friend, “and the better way to do it would be to assume that if you wanted to develop a therapy for prevention, shouldn’t you look at those who should have gotten sick and didn’t.”

Friend, who has had successful turns as a cancer researcher, a biotech CEO, and the head of cancer research at , calls the effort, called The Resilience Project, one of the most exciting he has ever been involved with.

The idea dates back to the work of Nobel laureate Lee Hartwell, with whom Friend started a biotech company in the 1990s. In February 2001 Hartwell wrote an article in Science proposing that researchers should worry more about what he called “buffering.”

Just having a gene variant, even for a terrible disease like cystic fibrosis, which fills the lungs with mucus, causes digestive problems, infertility, and early death, may not always mean you get sick. Geneticists call this “penetrance” - the trait a gene codes for may not penetrate into the physical symptoms of a person. This, Hartwell argues, is because there are probably other gene variants in the body that are keeping the bad gene from doing harm.

Nice theory. But why does Friend think finding these genes is even plausible? Because he did a test run. He teamed up with Eric Schadt, who worked for Friend at Merck and now directs the Icahn Institute for Genomics and Multiscale Biology at the Mount Sinai School of Medicine. They were able to get anonymized samples from more than half a million people from databases including the one kept by genetics startup 23andMe, and from them they found 10 people who seem to carry genes that cause 12 diseases, including rare but deadly diseases cystic fibrosis, Gaucher’s disease, and MPS II. Friend calls them “unexpected heroes:” people whose genomes may hold hints at how to prevent disease.

The problem: because of the way the data were collected, they can’t easily go back to those people to study them. So they need to start the search anew. “All we need is information,” Friend says in his TED talk. “We need a swab of DNA and a willingness to say, what's inside me? I'm willing to be re-contacted.” Patients can sign up through the project’s web site.

Even once those people are found, the effort won’t be over. “It’s a big challenge,” says Daniel Macarthur, a genomics researcher at Massachusetts General Hospital. The unexpected heroes will be so small in number that traditional genetics won’t be able to find the protective genes. Instead, Friend and Schadt say, they will put those people’s genes in model organisms like mice. They will create induced pluripotent stem cells of the heroes’ DNA, and study those. Other groups will study their cells using new techniques like CRISPR, which allows scientists to do targeted genetic editing to figure out what happens when particular changes are made to a cell’s DNA.

If the effort comes up dry on finding protective genes, MacArthur says, just learning more about how often disease genes actually cause disease will be hugely useful for scientists.

But genes are not destiny not only because of other genes, but because of environmental factors, too. Friend and Schadt have tied up with the National Institute of Environmental Health Sciences. Linda S. Birnbaum, the Institute’s director, says that the effort could be “a treasure-trove for geneticists, epidemiologists, biostatisticians, and potentially all biomedical researchers.”

“Most people think of your genes, heredity, and environment as risks,” Friend says. “There’s this fear among the public that you would never want to know what is going on, that the genes are all bad. What we’re trying to say is we would never be here if there weren’t for this point of power we bring with us: Not the bad mutations but the good that actually allow us to survive.”